High Risk Factors For Recurrence Research Articles

Adjuvant chemotherapy in clinical local advanced CRC following preoperational therapies and pT0-3N0M0 diagnosis (CANWATCH).

TPS3645 Background: Adjuvant chemotherapy is often deemed unnecessary in pathological stage II colorectal cancer (CRC) following initial surgery without high-risk factors for recurrence. However, the efficacy of adjuvant chemotherapy for pT1-3N0M0 CRC following preoperative chemotherapy or chemoradiotherapy remains uncertain. Some cases of clinical locally advanced CRC (cTxN1-2M0), which are down-staged to pT0-3N0M0 after preoperative chemotherapy or chemoradiotherapy, may not truly require adjuvant chemotherapy due to the down-staging effects of preoperative treatments or false-positive imaging diagnosis of lymph nodes. Methods: CANWATCH is a multicenter, open-label, randomized, phase III study with a parallel design conducted in China. Patients were randomly assigned (1:1) to the wait-and-watch group or the adjuvant chemotherapy group. Enrollment and random assignment were performed using a computerized randomization management system. Patients in the wait-and-watch group did not receive adjuvant chemotherapy but were followed up periodically, while patients in the adjuvant chemotherapy group continued to receive adjuvant chemotherapy based on 5-FU or 5-FU analogues (mFOLFOX6 or Capeox). This study is the first prospective randomized controlled study to assess the necessity of adjuvant chemotherapy for patients with locally advanced CRC who received neoadjuvant therapy and achieved a down-staging to pT0-3N0M0. The study aims to provide precise clinical evidence for individualized precision treatment in locally advanced CRC patients. Key inclusion criteria included preoperative clinical tumor stage III (cTxN1-2M0) CRC, pathologically confirmed CRC adenocarcinoma by endoscopic biopsy, postoperative pathological stage T0-3N0M0 without high-risk factors for recurrence, and patient ability to understand and sign written informed consent. Main exclusion criteria were a history of other malignant tumors, complications requiring emergency surgery (occlusion, sub-occlusion, massive hemorrhage, and abscesses), colorectal tumor extension toward the abdominal wall and/or adjacent organs preventing immediate R0 resection of liver metastases, non-resectable lymph node metastasis, American Society of Anesthesiologists (ASA) grading ≥ IV, and/or Eastern Cooperative Oncology Group (ECOG) score ≥ 2. A total of 650 patients are planned to be enrolled in this study, and 301 patients have been enrolled as of February 6, 2024. The study is registered with ClinicalTrials.gov (NCT03748485) and is ongoing. Clinical trial information: NCT03748485 .

Efficacy and safety of chemotherapy as monotherapy in patients with recurrent intermediate/high-risk factors following radical hysterectomy for stage IB-IIA cervical cancer: a single-center retrospective analysis

ObjectiveThe aim of this study is to explore the efficacy and safety of chemotherapy (CT) as a monotherapy in patients with recurrent intermediate/high-risk factors following radical hysterectomy for stage IB-IIA cervical cancer.MethodsA retrospective analysis was conducted on the medical records of patients diagnosed with stage IB-IIA cervical cancer who underwent radical hysterectomy at the People’s Hospital of Suzhou High-tech District between 2010 and 2020. A total of 66 patients with intermediate or high-risk factors for recurrence were treated exclusively with CT. This cohort included 42 patients in the intermediate-risk group and 24 in the high-risk group. Treatment protocols consisted of 4–6 cycles of paclitaxel and cisplatin drugs for the intermediate-risk group, and 6 cycles for the high-risk group. The relapse-free survival (RFS), recurrence rates, and common CT-related adverse reactions, including bone marrow suppression, nausea and vomiting, and diarrhea, were assessed for both groups.Results(1) The cumulative 3-year RFS rates for the intermediate-risk and high-risk groups were 97.3% (36/37) and 82.4% (14/17), respectively, with cumulative 5-year RFS rates of 97.1% (34/35) and 82.4% (14/17), respectively. The Log rank test revealed no significant difference between the two groups (P > 0.05), (χ² = 2.718, P = 0.099). The 5-year recurrence rates in the intermediate-risk and high-risk groups were 2.38% (1/42) and 12.50% (3/24), respectively. (2) The incidence of grade III bone marrow suppression in the intermediate-risk and high-risk groups was 21.19% (11/42) and 25.00% (6/24), respectively, while the incidence of grade IV bone marrow suppression was 11.90% (5/42) and 8.33% (2/24), respectively. There was no statistically significant difference in bone marrow suppression grades between the two groups (P > 0.05).ConclusionCT with paclitaxel and cisplatin, administered as monotherapy post-radical hysterectomy for stage IB-IIA cervical cancer, demonstrates satisfactory survival benefits with an acceptable safety profile. Moreover, no significant differences were observed in prognosis or adverse reactions between the different risk groups treated solely with CT.

Update results from ALTER-H004 study: Anlotinib combined with TACE as adjuvant therapy in patients with hepatocellular carcinoma (HCC) at high risk of recurrence after surgery: A single arm, multi-center, phase II clinical trial.

513 Background: High recurrence rate after curative resection significantly compromised the long-term survival of patients with HCC patients (pts). TACE as adjuvant therapy was proved to improve clinical outcomes for pts with high recurrence risk factors after hepatectomy. However, the prognosis of TACE reminded unsatisfactory and controversial. Therefore, this study aimed to identify the efficacy and safety of anlotinib as maintenance adjuvant treatment following inductional TACE in pts with HCC. The update results were reported here with longer follow-up duration. Methods: HCC pts with one of the following high risk factors after hepatectomy: ≥5 cm and <10 cm of tumor diameter, tumor number ≥3, tumor microvascular invasion M1 or M2, portal vein tumor thrombus resection (Cheng's classification I/II) were recruited. Eligible pts received cTACE treatment within 1-2 months after hepatectomy, on the 3-5th day after cTACE, oral anlotinib (12mg, qd, d1-d14, q3w) was given until disease recurrence or unacceptable toxicity. The predefined sample size was 30. The primary endpoint was disease free survival (DFS). Secondary endpoints included 1-year DFS rate, time to recurrence and safety. Results: The data cut-off date was March 2023, 29 pts were enrolled and 27 pts received at least once tumor assessment. The median follow-up was 21.8 (IQR, 17.3-26.3) months. Of 27 with assessable efficacy, mDFS was 24.2 (95% CI, not applicable-not applicable) months, with 12-, and 24-month DFS rates of 72.2% (95% CI, 50.4%-85.7), and 61.8% (95% CI, 38.8%-78.3%), respectively. 18 of 27 pts (66.7%) experienced treatment-related adverse events (TRAEs). Grade 3 TRAEs occurred in 4 pts (14.8%) included hypertension (7.4%), leukocytopenia (7.4%) and ascites (3.7%). No grade 4 or 5 TRAEs occurred. Conclusions: Anlotinib combined with TACE as adjuvant therapy in HCC pts at high recurrence risk exhibited encouraging efficacy and tolerable safety profile. And the conclusions needed to be confirmed in large scale clinical trials subsequently. Clinical trial information: NCT04213118 .

Preliminary results of ALTER-H006: A phase II study of TQB2450 plus anlotinib as adjuvant therapy in hepatocellular carcinoma (HCC) with high risk of recurrence after radical resection.

494 Background: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death. Surgical resection remains as the mainstay of curative treatment option, However, the recurrence rate after surgical resection could be high especially in patients with CNLC stage IIb (tumor number ≥ 4) and IIIa (vascular invasion). Herein we evaluated the efficacy and safety of the anti-angiogenic tyrosine kinase inhibitor, anlotinib, plus TQB2450, a novel programmed death-ligand 1 (PD-L1) inhibitor as an adjuvant treatment for HCC with high risk of recurrence after radical resection. Methods: This prospective, multiple-center, single-arm phase II study (NCT05111366) enrolled histologically confirmed resectable HCC pts for CNLC Stage IIb/IIIa with any of the following high-risk factors for recurrence: a) tumor nodules ≥4; b) portal vein tumor thrombus (PVTT): vp1 or vp2; c) hepatic vein tumor thrombus (HVTT): vv1 or vv2. At 4-8 weeks after R0 resection, adjuvant therapy was started with anlotinib (12 mg, p.o., qd, d1-14, q3w) plus TQB2450 (1200 mg, i.v., d1, q3w) until disease recurrence or unacceptable toxicity or up to 18 cycles (~1 year). Primary endpoint was 1-year recurrence-free survival (RFS) rate; secondary endpoints were RFS, 1-year overall survival (OS) rate, and safety. Results: Between January 2022 and August 2023, a total of 22 pts from 4 centers were enrolled, 21 pts included in per-protocol set analysis. The 21 pts were predominantly male (95 %, n = 20), and the median age was 50 years (range: 33–75). Eight pts (38%) had CNLC Stage IIb and 13(62%) had CNLC Stage IIIa HCC. Among them, 19 pts received at least once tumor assessment. According to RECIST 1.1, out of 21 pts, 16 showed no recurrence, 3 relapsed, 1 dropped out and 1 discontinued due to serious adverse events. The 1-year RFS rate was 62.31%（95%CI: 17.15-88.08）, while the median RFS was not mature. Additionally, safety profile exhibited that the regimen was tolerable. 16 of 22 pts (73%) experienced treatment-related adverse events (TRAEs). Grade 3 TRAEs occurred in 6 pts (27 %) including hypertension (13.5 %), neutropenia (9 %), and bleeding (4.5 %). Conclusions: The present study indicated that anlotinib plus TQB2450 as adjuvant treatment for HCC with high risk of recurrence after radical resection exhibited potential efficacy and tolerable safety profile. The conclusion should be validated in more participants included subsequently. Clinical trial information: NCT05111366 .

Influence of adjuvant chemotherapy on survival for patients with completely resected high-risk stage IB NSCLC

BackgroundThe use of adjuvant chemotherapy (ACT) in completely resected stage IB NSCLC is still controversial. This study aims to investigate the efficacy of ACT in pathological stage IB non-small cell lung cancer (NSCLC) with high risk factors.MethodsPatients with pT2aN0M0 stage IB NSCLC who underwent complete resection from 2013 to 2017 were retrospectively analyzed. Univariate and multivariable logistic regression analysis was used to assess potential independent risk factors associated with poor prognosis. To compare survival between patients who received ACT and those who did not.ResultsIn univariate and multivariate analyses, adenocarcinomas with predominantly micropapillary (MIP) and solid patterns (SOL), poorly differentiated squamous cell carcinoma (SCC), number of lymph nodes dissected less than 16 and tumor size larger than 36 mm were identified as high-risk factors for recurrence. In patients with high risk factors for recurrence, ACT resulted in significantly longer DFS (HR, 0.4689, 95%CI, 1.193–3.818; p = 0.0108) and OS (HR, 0.4696, 95%CI, 0.6578–6.895; p = 0.2073), although OS failed to reach statistically significance. After propensity score matching (PSM), 67 pairs of patients were 1:1 matched in the two groups and all baseline characteristics were well balanced. The results also demonstrated that ACT was associated with improved DFS (HR, 0.4776, 95%CI, 0.9779–4.484; p = 0.0440) while OS was not significantly different (92.5% vs. 91.0%; HR, 0.6167, 95%CI, 0.1688–2.038; p = 0.7458). In patients with low-risk factors for recurrence, DFS (HR, 0.4831, 95%CI, 0.03025-7.715; p = 0.6068) and OS (HR, 0.969, 95%CI, 0.08364-11.21; p = 0.9794) was not significantly different between those who received ACT and those who did not.ConclusionIn patients with completely resected stage IB NSCLC, ACT can improve survival in patients with high risk for recurrence. Further large multicenter studies are needed to confirm these findings.

A prospective, single-arm, phase II clinical study of tislelizumab in combination with lenvatinib for perioperative treatment of resectable primary hepatocellular carcinoma with high risk of recurrence.

e16218 Background: Surgery is the main radical treatment for hepatocellular carcinoma (HCC), but the high postoperative recurrence rate makes the survival benefit of patients limited. Neoadjuvant therapy mainly reduces postoperative recurrence by controlling micrometastasis and reducing preoperative tumor load and other high recurrence risk factors, but there are limited data on its application in liver cancer. Tislelizumab, a PD-1 monoclonal antibody, has shown promising efficacy with acceptable safety profile in combination with lenvatinib in the first-line treatment of advanced HCC. This study aims to explore the safety and feasibility of tislelizumab combined with lenvatinib in the neoadjuvant therapy and adjuvant therapy of resectable HCC. Methods: This prospective, single-center, single-arm phase II study (NCT04834986) enrolled patients with histologically confirmed resectable HCC who were at high risk of recurrence, as assessed by the investigators before surgery. Patients did not have any medical treatment in the past, with ECOG of 0-1, and had adequate organ and bone marrow function. Eligible patients received 4 cycles with tislelizumab (200mg, d1, Q3W) combined with Lenvatinib (8mg/kg, PO, qd) and surgery was performed within 4 weeks after treatment. At 4-8 weeks after surgery, adjuvant therapy was started with tislelizumab (200mg, d1, Q3W) and lenvatinib (8mg/kg, PO, qd) for at least half a year or until disease progression or intolerance of adverse reactions. Primary endpoints were safety and feasibility; secondary endpoints were ORR, 1 and 2-years DFS%, pCR, and DFS. Results: From Sep 7,2021 to Nov 9,2022, 24 patients (median age, 57.5 years) were enrolled, with most patients were males (95.8%) and 22 patients (91.7%) had HBV infection. All patients had Child-Pugh grade A and ECOG PS 0. The median treatment period was 4 cycles. In 24 patients, 17 patients (70.8%) underwent R0 resection, 3 patients (3/17, 17.6%) achieved complete pathological response (PCR), and 6 patients (6/17, 35.3%) achieved major pathological response rate (MPR, necrosis > 70%). 3 patients (12.5%) had significant tumor shrinkage and refused surgery. 1 patient (4.2%) is waiting surgery. 3 patients (12.5%) developed disease progression. According to RECIST1.1, ORR was 54.2% (13/24, CR 1, PR 12), DCR was 87.5%. According to mRECIST, ORR was 75.0% (18/24, CR 6, PR 12), DCR was 87.5%. No grade 3 or above adverse events were observed during neoadjuvant treatment period. The most common adverse events of any grade were rash (14/24,58.3%), hypertension (5/24,20.8%) and diarrhea (4/24,16.7%). Conclusions: Tislelizumab in combination with lenvatinib was well tolerated and showed promising efficacy as a neoadjuvant therapy for resectable HCC with high risk of recurrence. Clinical trial information: NCT04834986 .

Super‐stable homogeneous embolic agents advance the treatment of hepatocellular carcinoma

Super‐stable homogeneous embolic agents advance the treatment of hepatocellular carcinoma

Adjuvant radiotherapy in the management of porocarcinoma with lymphatic micrometastasis

Background. Porocarcinoma is a rare skin tumor originating from dermal sweat glands. Surgical procedures are the first choice of treatment, but the role of adjuvant therapies, such as chemotherapy and radiotherapy (RT), is not clear. In this case report and review of the literature, we aimed to present a patient who underwent adjuvant RT for the diagnosis of porocarcinoma with lymphatic micrometastasis and a review of the current literature. Case summary. A 61-year-old male was admitted to the dermatology department for a nodular lesion on the left knee skin. An excisional biopsy was performed, and the pathology result was reported as porocarcinoma. The closest surgical margin of the tumor was 0.2 cm. In the inguinal sentinel lymph node sampling, two of the three removed lymph nodes had micrometastases. Then, adjuvant RT was applied to the left inguinofemoral lymphatics and primary tumor bed. No recurrence was observed in the patient with a follow-up period of 24 months. No acute or late toxicity was observed including lymphedema, subcutaneous fibrosis, or stiffness of the knee joint. Conclusions. Although adjuvant RT is not a routinely recommended treatment, it can be applied to increase local and regional control in patients with high-risk factors for recurrence or with lymph node metastases. There is a great need for clinical studies clarifying the role of RT, but for now, all patients should undergo multidisciplinary evaluation when a decision on adjuvant therapies is made.

Adjuvant therapy following curative treatments for hepatocellular carcinoma: current dilemmas and prospects.

Curative surgical treatments, mainly liver resection, are still one of the optimal options for patients with early-, mid-, and even progression-stage hepatocellular carcinoma (HCC). However, the recurrence rate within 5 years after surgery is as high as 70%, especially in patients with high risk factors for recurrence, most of whom experience early recurrence within 2 years. Effective adjuvant therapy may improve prognosis, previous studies found that adjuvant transarterial chemoembolization, antiviral, and traditional Chinese medicine etal. were helpful in preventing HCC recurrence. Nevertheless, due to controversial results or lack of high-level evidence, there is no standardized postoperative management protocol worldwide at present. Continued exploration of effective postoperative adjuvant treatments to improve surgical prognosis is necessary.

Risk Factors for Recurrence of Stage I Epidermal Growth Factor Receptor Mutated Lung Adenocarcinoma

BackgroundWe aimed to clarify the risk factors for postoperative recurrence in patients with epidermal growth factor receptor (EGFR)-mutated stage I lung adenocarcinoma, using EGFR wild-type adenocarcinoma as a comparator, to select optimal candidates for adjuvant therapy with EGFR tyrosine kinase inhibitor (TKI). MethodsData of patients with pathologic stage I EGFR-mutated (n = 713) and wild-type (n = 673) adenocarcinoma who did not receive adjuvant therapy were retrospectively analyzed. The cumulative incidence of recurrence (CIR) was estimated using Gray’s method, and multivariable Fine-Gray competing risk models identified independent risk factors associated with recurrence. ResultsThe CIR did not differ significantly between patients with EGFR-mutated and wild-type adenocarcinoma (P = .32). Multivariable analysis revealed that greater size (cm) of invasive tumor (hazard ratio 1.539; 95% CI, 1.077-2.201), lymphovascular invasion (hazard ratio 5.180; 95% CI, 2.208-12.15), pleural invasion (hazard ratio 3.388; 95% CI, 1.524-7.533), and high-grade histologic subtype (hazard ratio 4.295; 95% CI, 1.539-11.99) were independent risk factors for recurrence in patients with EGFR-mutated adenocarcinoma. The 5-year CIR was significantly higher among patients with these factors (tumor size greater than 2 cm, 15.9%; lymphovascular invasion, 26.9%; pleural invasion, 39.3%; and high-grade subtype, 44.4%) than among patients without them (4.4%, 2.2%, 3.9%, and 5%, respectively; P < .001). For patients with EGFR wild-type adenocarcinoma, independent risk factors for recurrence were invasive tumor size, lymphovascular invasion, and pleural invasion, but not histologic subtypes. ConclusionsEven for patients with EGFR-mutated stage I lung adenocarcinoma, recurrence risk is stratified. Adjuvant therapy may be considered if they have high-risk factors for recurrence.

ALTER-H006: A phase II study of TQB2450 plus anlotinib as adjuvant therapy in hepatocellular carcinoma (HCC) with high risk of recurrence after surgical resection.

TPS632 Background: Recurrence rate at 5 years for patients with early-stage HCC undergoing resection is between 50% and 70%. The optimal adjuvant treatment strategy for patients with resected HCC has not been proved and there is limited evidence to support a standard regimen for adjuvant treatment. Anlotinib, an oral small molecule antiangiogenic inhibitor, has shown promising anti-tumor activity and manageable toxicity as first or second-line treatment for patients with advanced HCC in an open-label phase II trial (NCT02809534). Anlotinib plus TQB2450, an anti-PD-L1 mAb, has shown anti-tumor activity in some solid tumors, such as biliary tract cancer (NCT03996408) and non-small cell lung cancer (NCT03910127). Here we investigate the efficacy and safety of this regimen as an adjuvant treatment for HCC with a high risk of recurrence after surgical resection. Methods: This is a single-arm, multicenter phase II trial. A total number of 37 patients with histologically or cytologically confirmed HCC will be enrolled. Eligible patients are aged 18-75, ECOG 0-1, Child-Pugh class A, 4~8 weeks after R0 resection with any of the following high-risk factors for recurrence: a) tumor nodules ≥4; b)portal vein tumor thrombus (PVTT): vp1 or vp2; c) hepatic vein tumor thrombus (HVTT): vv1 or vv2. Patients enrolled receive anlotinib (12 mg, p.o., qd, d1-14, q3w) plus TQB2450 (1200 mg, i.v., d1, q3w) until disease recurrence or unacceptable toxicity or up to 18 cycles (~1 year), whichever occurs first. Tumor assessment is performed at the end of the second cycle and every four cycles since that, according to RECIST v1.1. The primary endpoint is 1-year recurrence-free survival (RFS) rate. Secondary endpoints include RFS, 1-year overall survival (OS) rate, and safety. Recruitment for this study began in January 2022. Clinical trial information: NCT05111366 .

Final analysis of a prospective controlled trial of the efficacy of uracil and tegafur/leucovorin for stage II colon cancer with risk factors for recurrence using propensity score-based methods (JFMC46-1201).

117 Background: The usefulness of adjuvant chemotherapy for stage II colon cancer with high-risk factors for recurrence has not been established. Methods: This was a prospective, non-randomized controlled study based on patients’ selection of treatment options, including randomized therapeutic decision-making. High-risk factors were defined as having at least one of the following factors: T4, perforation/penetration, poorly differentiated adenocarcinoma/mucinous carcinoma, and &lt; 12 dissected lymph nodes. UFT (300 mg/m2/day) plus LV (75 mg/day) were orally administered for 6 months after surgery. The primary endpoint was disease-free survival (DFS) after adjusting for risk factors using propensity sore matching (1:2) and inverse probability of treatment weighting (IPTW) in the non-randomized arm. The secondary endpoints were overall survival (OS) and safety. Results: 1902 (98%) and 36 (2%) patients were enrolled in the non-randomized and randomized arms, respectively between May 2012 and April 2016. There were too few patients in the randomized arm and these were therefore excluded from the analysis. Eligible patients were divided into two groups: A, patients who selected surgery alone (n = 641); B, patients who selected UFT/LV treatment (n = 1239). Of the eligible patients, 402 in group A and 804 in group B were propensity score-matched. The 5-year DFS rate (95% confidence interval) was significantly higher in group B (76.3% [73.1-79.1]) than in group A (68.8% [63.9-73.2]) {hazard ratio [HR] 0.66 [0.51–0.84, P = 0.0008]}. The 5-year OS rates were not significantly different between group B and group A [HR 0.74 (95% CI 0.50–1.10, P = 0.1391)]. Using IPTW, significantly higher 5-year DFS [HR 0.71 (95% CI 0.59–0.86, P = 0.0006)] and overall survival [HR 0.66 (95% CI 0.49–0.90, P = 0.0122)] rates were observed in group B compared with group A. Multivariate analysis revealed that male sex, over 70 years old, T4, &lt; 12 dissected lymph nodes, and no adjuvant chemotherapy were significant risk factors for recurrence. Conclusions: Adjuvant chemotherapy with UFT/LV significantly improves DFS. Oral UFT/LV as adjuvant chemotherapy shows efficacy with an acceptable safety profile for stage II colon cancer with risk factors. Clinical trial information: UMIN000007783 .

Homoharringtonine-Based Induction Therapy Reduces the Recurrence Rate of Pediatric Acute Myeloid Leukemia After Allogeneic Hematopoietic Stem Cell Transplantation.

Allogeneic hematopoietic stem cell transplantation (HSCT) is an effective treatment for acute myeloid leukemia (AML). Pediatric patients with AML who relapse after HSCT have an extremely poor prognosis. We performed a retrospective study of pediatric patients diagnosed with AML from August 2015 to October 2019 who were treated with HSCT. Kaplan-Meier analyses were used to evaluate overall survival (OS), event-free survival (EFS), and cumulative recurrence rate (CRR). Cox regression analysis was used to determine the association between the baseline characteristics and relapse. A total of 37 pediatric patients met the inclusion criteria. Twenty-eight (75.7%) patients survived, and 9 (24.3%) patients died. The OS rates of AML patients treated with HSCT were 89.2% ± 5.1%, 75.7% ± 7.1%, and 75.7% ± 7.1% at 1, 3, and 5 years, respectively, and the CRRs were 11.4% ± 5.4%, 24.7% ± 7.7%, and 33.1% ± 10.4% at 1, 3, and 5 years after HSCT, respectively; four of nine children who relapsed after transplantation died. Induction with etoposide rather than homoharringtonine and fungal infections could be high-risk factors for recurrence after transplantation. The association between homoharringtonine-based induction therapy and a low recurrence rate persisted after adjusting for age, sex, risk stratification, fusion genes, and fungal infections. This study clarifies the clinical features and poor prognosis of post-transplant relapse in pediatric AML and indicates the urgent need for effective therapy for patients who relapse after HSCT.

Short-Course Radiotherapy Based Total Neoadjuvant Therapy Combined with Toripalimab for Locally Advanced Rectal Cancer: Preliminary Findings from a Randomized, Prospective, Multicenter, Double-Arm, Phase II Trial (TORCH)

<h3>Purpose/Objective(s)</h3> For patients with locally advanced rectal cancer (LARC), the standard treatment is neoadjuvant chemoradiotherapy combined with curative surgery. Total neoadjuvant therapy (TNT) has been used to increase rates of complete response and organ preservation, and achieve early control of distant metastasis. Recently, hypofractionated radiotherapy shows better synergistic effects in combination with PD-1/PD-L1 antibodies than conventional fractionated radiotherapy. Thus, the combination of short-course radiotherapy (SCRT) based TNT and immunotherapy is likely to further improve both tumor response and prognosis for LARC patients. <h3>Materials/Methods</h3> TORCH is a randomized, prospective, multicenter, double-arm, phase II trial. 130 LARC (T3-4/N+M0, distance from anus ≤10cm) patients will be treated with TNT approach and assigned to the consolidation arm (A) and induction arm (B). Arm A will receive SCRT (25 Gy/5Fx), followed by 6 cycles of Toripalimab plus capecitabine and oxaliplatin (ToriCAPOX). Arm B will first receive 2 cycles of ToriCAPOX, then receive SCRT, followed by 4 cycles of ToriCAPOX. Both groups will receive curative surgery or W&W strategy. The primary endpoint is the rate of complete response (CR, pCR plus cCR). The secondary endpoints include the grade 3-4 acute adverse effects (AE) rate, 3-year DFS rate, 3-year OS rate, etc. The "pick the winner" method is used to investigate the better regimen. <h3>Results</h3> Up to February 20, 2022, 81 patients have been recruited in the trial. A total of 16 patients (all MSS; arm A: 7, arm B: 9) have completed all neoadjuvant therapy. Most of them showed high risk factors of recurrence, including lower location (≤5cm, 14/16), deeper primary lesion invasion (cT4/MRF+, 7/16) and more positive lymph nodes (cN2, 9/16). Finally, 5 patients (arm A: 1, arm B: 4) achieved cCR and decided to adopt W&W strategy. 11 patients received surgery (Dixon: 6, Miles: 5) and the pathological results showed 8 cases of pCR (arm A: 4, arm B: 4), one near-pCR (arm A) and two non-pCR (arm A: 1, arm B: 1). Thus, the CR rate was amazingly high (CR rate: 81.25%, 13/16; pCR rate: 72.73%, 8/11). Even 6 patients who were evaluated as ycT3/N+/MRF+/EMVI+ before surgery was still demonstrated to be pCR after strict pathological examination. The only grade 3 AE was thrombocytopenia (37.50%, 6/16). And no grade 4 AE was observed. <h3>Conclusion</h3> SCRT base TNT combined with Toripalimab have achieved surprisingly excellent CR rate and good tolerance in LARC patients (in our cohort), which has the potential to improve organ preservation rate. In the future, this ongoing trial will demonstrate this efficacy and compare the two arms by larger sample size.

The Failure Patterns of Nasopharygeal Carcinoma After Intensity-Modulated Radiotherapy and Implications for Surveillance.

ObjectiveTo investigate the treatment outcomes, failure patterns and surveillance strategy in patients with nasopharyngeal carcinoma (NPC) after intensity-modulated radiotherapy (IMRT).MethodsA cohort of patients with NPC who had received the full course of IMRT between 2008 and 2012 were retrospectively analyzed. The failure patterns, time to recurrence, and detection methods were recorded. The survival was calculated using the Kaplan–Meier method. Multivariate proportional hazard regression models were used to test the prognostic factors.ResultsIn total, 2607 patients with NPC treated with IMRT were recruited. After the median follow-up of 112 months, 402 (15.4%) patients experienced distant metastasis, 225 (8.6%) patients had local recurrence, and 77 (3.0%) patients had regional recurrences. The 10-year overall survival (OS), local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) rates were 74.5%, 90.1%, and 79.3%, respectively. The factors of male sex, age >50 years, lactate dehydrogenase >245 IU/L, advanced T classification, and advanced N classification were associated with poor OS. The N disease classification was the most important factor in predicting distant metastasis, and advanced T disease classification for high risk of local recurrence. For patients with T1 disease, the incidence of local recurrence was less than 2%, and the incidence of distant metastasis was less than 5% for patients with N0 disease. About 83% of the recurrence occurred in the first 5 years, and 20% of the recurrences showed no symptoms.ConclusionHigh rate of local-regional control can be achieved for patients with NPC after IMRT, while distant metastasis remains as the major cause of failures. Patients with advanced N classification has high risk to develop distant metastasis, and most occurred within 5 years. Developing rational and individualized surveillance strategies based on the high risk factors of recurrence is helpful to balance the survival benefit and medical cost.

The Role of Conization before Radical Hysterectomy in Cervical Cancer including High Risk Factors of Recurrence: Propensity Score Matching.

Simple SummaryWe investigated the therapeutic role of conization prior to radical hysterectomy for stage IB1 to IIB cervical cancer regardless of pathologic high risk factors, using the propensity score matching method. Additional subgroup analysis was carried out to identify the effect of conization based on clinical and pathologic factors. Conization before radical hysterectomy was associated with reduced recurrence and mortality. Conization had benefit in patients with MIS, negative pelvic lymph nodes, tumor sized less than 4 cm. Delays of definite treatment due to conization did not have an effect on the prognosis of patients with high risk factors. This study reveals the protective role of preoperative conization in early-stage cervical cancer, along with identifying subgroups that may best benefit from the procedure. This information can be used for more tailored patient selection for minimally invasive surgery for cervical cancer.We primarily aimed to investigate the therapeutic role of conization prior to radical hysterectomy for cervical cancer. Secondarily, we aimed to characterize a subgroup of patients who could potentially benefit from preoperative conization. Patients who underwent radical hysterectomy for FIGO 2009 stage IB1 to IIB cervical cancer from 1995 to 2020 were eligible. The patients were divided into two groups: those with and without preoperative conization. To adjust for the baseline characteristics of the two groups, 1:2 case–control propensity score matching was conducted. Survival analysis was performed between the two groups. Subgroup analysis was performed to identify the effect of conization based on clinical and pathological factors. Patients who underwent preoperative conization showed better 5-year overall survival than those who did not (95.9% vs. 93.0%, p = 0.029); however, no difference was observed in progression-free survival (88.9% vs. 85.9%, p = 0.155). In multivariate Cox analysis, conization showed a 55% reduction in recurrence (hazard ratio (HR) 0.65, 95% confidence interval (CI) 0.41–1.01, p = 0.056) and 41% reduction in death (HR 0.59, 95% CI 0.34–1.02, p = 0.059), but with marginal statistical significance. In subgroup analysis, minimally invasive surgery (MIS), negative pelvic lymph node, and tumor size < 4 cm showed improved survival from conization. Conization before radical hysterectomy may be associated with improved survival in patients with early-stage cervical cancer. This information could serve as a basis for a more tailored patient selection for MIS for cervical cancer.

Hormone Therapy Reduces Recurrence in Stage II-IV Uterine Low-Grade Endometrial Stromal Sarcomas: A Retrospective Cohort Study.

Low-grade endometrial stromal sarcoma (LG-ESS) is a rare and indolent malignancy. Hormone therapy has been reported as an adjuvant treatment for LG-ESS, although its effectiveness is controversial. Here we aimed to investigate the effects of postoperative hormone therapy on recurrence in patients with uterine LG-ESS. Between January 2010 and December 2019, a total of 152 patients (23 with and 129 without fertility-sparing) with a diagnosis of primary uterine LG-ESS confirmed by pathologists were enrolled in this study. In the cohort without fertility-sparing, 22 (17.7%) patients had recurrence, and the median disease-free survival (DFS) was 47 (2-130) months; only one of these patients died of LG-ESS. No significant difference was found in recurrence between the groups with and without hormone therapy (p=0.802). However, subgroup analysis showed that hormone therapy decreased the recurrence rate in stage II-IV (p=0.001, HR 0.144, 95% CI: 0.038-0.548), but not in stage I disease (p=0.256). High-dose progestins notably reduced recurrence (p=0.012, HR 0.154, 95% CI: 0.036-0.660), whereas non-progestin therapy marginally influenced recurrence (p=0.054) compared with no hormone therapy in stage II-IV disease. Moreover, hormone therapy within 12 months was effective in reducing recurrence (p=0.038, HR 0.241, 95% CI: 0.063-0.922). Ovarian preservation (p=0.004, HR 6.250, 95% CI: 1.786-21.874) and negative expression of ER/PR (p=0.000, HR 23.249, 95% CI: 4.912-110.026) were high-risk factors for recurrence in patients without fertility-sparing. In the fertility-sparing cohort, 15 (65.2%) patients experienced recurrence, and the median DFS was 24 (3-107) months. Six patients successfully delivered healthy fetuses, and five received hormone therapy. Twelve patients finally accepted hysterectomy after repeated recurrence, and only two of them had given birth before surgery. Patients who received hormone therapy showed longer DFS, although this difference was not statistically significant (p=0.466). In conclusion, postoperative hormone therapy reduces recurrence in patients with stage II–IV uterine LG-ESS without fertility-sparing, and high-dose treatment with progestins within 12 months is recommended. Bilateral oophorectomy can also reduce the risk of recurrence. Patients with fertility-sparing have a high risk of recurrence and poor pregnancy outcomes, and hormone therapy may be a reasonable choice in postoperative management.

Short-course radiotherapy combined with CAPOX and toripalimab for the total neoadjuvant therapy of locally advanced rectal cancer: Preliminary findings from a randomized, prospective, multicenter, double-arm, phase II trial (TORCH).

e15602 Background: For patients with locally advanced rectal cancer (LARC), the standard treatment is neoadjuvant chemoradiotherapy combined with curative surgery. Total neoadjuvant therapy (TNT) has been used to increase rates of complete response and organ preservation, and achieve early control of distant metastasis. Recently, hypofractionated radiotherapy shows better synergistic effects in combination with PD-1/PD-L1 antibodies than conventional fractionated radiotherapy, as well as less impact on peripheral lymphocytes and more abscopal effects. Thus, the combination of immunotherapy and short-course radiotherapy (SCRT) based TNT is likely to further improve both tumor response and prognosis for LARC patients. Methods: TORCH is a randomized, prospective, multicentre, double-arm, phase II trial. 130 LARC (T3-4/N+M0, distance from anus ≤10cm) patients will be treated with TNT approach and assigned to the consolidation arm (A) and induction arm (B). Arm A will receive SCRT (25Gy/5Fx), followed by 6 cycles of Toripalimab plus capecitabine and oxaliplatin (ToriCAPOX). Arm B will first receive 2 cycles of ToriCAPOX, then receive SCRT, followed by 4 cycles of ToriCAPOX. Both groups will receive curative surgery or W&amp;W strategy. The primary endpoint is the rate of complete response (CR, pCR plus cCR). The secondary endpoints include the grade 3-4 acute adverse effects (AE) rate, 3-year DFS rate, 3-year OS rate, etc. The “pick the winner” method is used to investigate the better regimen. Results: Up to Jan 20th 2022, 67 patients have been recruited in the trial (arm A: 35; arm B: 32). A total of 11 patients (all MSS) have completed all neoadjuvant therapy. Most of them showed high risk factors of recurrence, including lower location (≤5cm, 10/11), deeper primary lesion invasion (cT4/MRF+, 6/11) and more positive lymph nodes (cN2, 6/11). Finally, 2 patients (both arm B) achieved cCR and received W&amp;W strategy. 9 patients received surgery and the pathological results showed 7 cases of pCR (arm A:3; arm B: 4), one near-pCR (arm A) and one non-pCR (arm A). Thus, the CR rate was amazingly high (CR rate: 81.8%, 9/11; pCR rate: 77.8%, 7/9). Even 5 patients who were evaluated as ycT3/N+/MRF+/EMVI+ before surgery was still demonstrated to be pCR after strict pathological examination. The only grade 3 AE was thrombocytopenia (4/11). And no grade 4 AE was observed. Conclusions: SCRT base TNT approach combined with Toripalimab have achieved surprisingly excellent CR rate and good tolerance in LARC patients (in our cohort), which has great clinical value in improving organ preservation. In the future, this ongoing trial will demonstrate this efficacy and compare the two arms by larger sample size. Clinical trial information: NCT04518280.

Update results from ALTER-H004 study: Anlotinib combined with TACE as adjuvant therapy in hepatocellular carcinoma patients at high risk of recurrence after surgery—A single-arm, multicenter, phase II clinical trial.

e16120 Background: Hepatectomy is considered to be an effective curative treatment for hepatocellular carcinoma (HCC), however, high recurrence rate after curative resection severely reduces the long-term survival of HCC patients (pts). Transarterial chemoembolization (TACE) as adjuvant therapy has been proved to improve clinical outcomes for pts with high recurrence risk factors after hepatectomy, but the effect is still unsatisfactory. ALTER-H004 trial was designed to evaluate the efficacy and safety of anlotinib as maintenance adjuvant treatment following inductional TACE in pts with HCC. Here we updated the results at the data cutoff of January 20, 2022. Methods: This single arm, multicenter, phase II trial of ALTER-H004 was planned to enroll 30 pts which with histologically confirmed HCC and undertook hepatectomy within 1-2 months. The recruited pts who did not recieve any previous tumor-related treatment must have any of the following high risk factors: ≥5 cm and &lt; 10 cm of tumor diameter, tumor number ≥3, tumor microvascular invasion M1 or M2, portal vein tumor thrombus resection (Cheng's classification I/II). Eligible pts received conventional TACE treatment within 1-2 months after hepatectomy. On the 3-5th day after TACE treatment, oral anlotinib (12mg, qd, d1-d14, q3w) was given until disease recurrence or unacceptable toxicity. The primary endpoint was disease free survival (DFS). Secondary endpoints included 1-year DFS rate, time to recurrence and safety. Results: By the cutoff date of January 20, 2022, 26 pts were enrolled and 25 pts received at least once tumor assessment. According to RECIST 1.1, 14 of 25 did not progress were still on treatment and 7 relapsed. One withdrew the consent and 3 discontinued because of intolerable adverse events. The longest duration of treatment is 16.53 months. The DFS were not mature and the 6-month DFS rates were 77.45% (95% CI: 53.83̃89.99). 12 of 25 pts (48.0%) experienced treatment-related adverse events (TRAEs). Grade 3 TRAEs occurred in 5 pts (20.0%) included hypertension (8.0%), leukocytopenia (8.0%) and ascites (4.0%). No grade 4 or 5 TRAEs occurred. Conclusions: The update results suggested that anlotinib combined with TACE as adjuvant therapy in HCC pts at high recurrence risk exhibited promising clinical benefit and favorable safety profile, and the results needed to be confirmed in trials continued subsequently. Clinical trial information: NCT04213118.

Analysis of the risk factor of insufficient examined lymph nodes in stage II colon cancer from the perspective of stage migration: A retrospective study combined with external validation

BackgroundAn insufficient examined lymph node (ELN) count is a high risk factor for recurrence in patients with stage II colon cancer (CC). This study aimed to explore this risk factor in relation to stage migration. MethodsWe screened 18,544 patients with stage II (pT3/4N0M0) and IIIB (pT3/4N1M0) CC diagnosed after radical resection from 2010 to 2015, using the National Cancer Institute Surveillance, Epidemiology, and End Results database. Propensity score matching was used to balance confounding factors for short-term and long-term survival, and survival analysis was carried out using the Kaplan–Meier method and log-rank test. The optimal cutoff for the number of ELNs in patients with stage II CC was determined using X-tile software. Independent prognostic factors were screened using Cox proportional hazards regression analysis. Finally, the results were externally validated in 318 patients with stage Ⅱ and ⅢB CC in our hospital from 2013 to 2015. ResultsThe best cutoff value for the number of ELNs in patients with stage II CC was 14. Multivariate analysis identified age, grade, histology, tumor size, T stage, N stage, ELN count, and chemotherapy as independent prognostic factors, and the Akaike and Bayesian information criteria values for the prognostic value of ELN count were relatively small. Patients with stage II CC with <15 ELNs had similar prognoses to patients with stage ⅢB CC (P = 0.939). Subgroup analysis and external validation yielded similar results. ConclusionPatients with stage II CC should be considered as stage ⅢB if the ELN count is insufficient.